Aims
The presence of diabetic foot ulcers is strongly associated with an increased risk of death. In this study, we investigate whether the effects of diabetes‐associated complications can explain ...the apparent relationship between diabetic foot ulcers and death.
Methods
We analysed data from 414 523 people with diabetes enrolled in practices associated with The Health Improvement Network in the United Kingdom. Our methods were designed to control for potential confounders in order to isolate the relationship between diabetic foot ulcers and death. Using proportional hazards models and the area under the receiver operator curve, we evaluated the effects of diabetic foot ulcers and the covariates on death.
Results
Among the patients, 20 737 developed diabetic foot ulcers; 5.0% of people with new ulcers died within 12 months of their first foot ulcer visit and 42.2% of people with foot ulcers died within 5 years. After controlling for major known complications of diabetes that might influence mortality, the correlation between diabetic foot ulcers and death remained strong with a fully adjusted hazard ratio of 2.48 (95% confidence interval: 2.43, 2.54). Geographic variance existed but was not spatially associated.
Conclusions
Diabetic foot ulcers are linked to an increased risk of death. This cannot be explained by other common risk factors. These results suggest that either there are major unknown risk factors associated with both diabetic foot ulcers and death, or that diabetic foot ulceration itself is a serious threat, which seems unlikely. A diabetic foot ulcer should be seen as a major warning sign for mortality, necessitating closer medical follow‐up.
What's new?
This is the largest patient cohort study ever to study the association between diabetic foot ulcers and risk of death in adults with diabetes.
Our findings support the hypothesis that diabetic foot ulcers are a marker associated with a risk to patients’ longevity independent of other complications of diabetes.
Neuroticism is a personality trait of fundamental importance for psychological well-being and public health. It is strongly associated with major depressive disorder (MDD) and several other ...psychiatric conditions. Although neuroticism is heritable, attempts to identify the alleles involved in previous studies have been limited by relatively small sample sizes. Here we report a combined meta-analysis of genome-wide association study (GWAS) of neuroticism that includes 91 370 participants from the UK Biobank cohort, 6659 participants from the Generation Scotland: Scottish Family Health Study (GS:SFHS) and 8687 participants from a QIMR (Queensland Institute of Medical Research) Berghofer Medical Research Institute (QIMR) cohort. All participants were assessed using the same neuroticism instrument, the Eysenck Personality Questionnaire-Revised (EPQ-R-S) Short Form's Neuroticism scale. We found a single-nucleotide polymorphism-based heritability estimate for neuroticism of ∼15% (s.e.=0.7%). Meta-analysis identified nine novel loci associated with neuroticism. The strongest evidence for association was at a locus on chromosome 8 (P=1.5 × 10(-15)) spanning 4 Mb and containing at least 36 genes. Other associated loci included interesting candidate genes on chromosome 1 (GRIK3 (glutamate receptor ionotropic kainate 3)), chromosome 4 (KLHL2 (Kelch-like protein 2)), chromosome 17 (CRHR1 (corticotropin-releasing hormone receptor 1) and MAPT (microtubule-associated protein Tau)) and on chromosome 18 (CELF4 (CUGBP elav-like family member 4)). We found no evidence for genetic differences in the common allelic architecture of neuroticism by sex. By comparing our findings with those of the Psychiatric Genetics Consortia, we identified a strong genetic correlation between neuroticism and MDD and a less strong but significant genetic correlation with schizophrenia, although not with bipolar disorder. Polygenic risk scores derived from the primary UK Biobank sample captured ∼1% of the variance in neuroticism in the GS:SFHS and QIMR samples, although most of the genome-wide significant alleles identified within a UK Biobank-only GWAS of neuroticism were not independently replicated within these cohorts. The identification of nine novel neuroticism-associated loci will drive forward future work on the neurobiology of neuroticism and related phenotypes.
Measurements of 21 cm Epoch of Reionization (EoR) structure are subject to systematics originating from both the analysis and the observation conditions. Using 2013 data from the Murchison Widefield ...Array (MWA), we show the importance of mitigating both sources of contamination. A direct comparison between results from Beardsley et al. and our updated analysis demonstrates new precision techniques, lowering analysis systematics by a factor of 2.8 in power. We then further lower systematics by excising observations contaminated by ultra-faint RFI, reducing by an additional factor of 3.8 in power for the zenith pointing. With this enhanced analysis precision and newly developed RFI mitigation, we calculate a noise-dominated upper limit on the EoR structure of Δ2 ≤ 3.9 × 103 mK2 at k = 0.20 h Mpc−1 and z = 7 using 21 hr of data, improving previous MWA limits by almost an order of magnitude.
Major depressive disorder (MDD) is a common complex disorder with a partly genetic etiology. We conducted a genome-wide association study of the MDD2000+ sample (2431 cases, 3673 screened controls ...and >1 M imputed single-nucleotide polymorphisms (SNPs)). No SNPs achieved genome-wide significance either in the MDD2000+ study, or in meta-analysis with two other studies totaling 5763 cases and 6901 controls. These results imply that common variants of intermediate or large effect do not have main effects in the genetic architecture of MDD. Suggestive but notable results were (a) gene-based tests suggesting roles for adenylate cyclase 3 (ADCY3, 2p23.3) and galanin (GAL, 11q13.3); published functional evidence relates both of these to MDD and serotonergic signaling; (b) support for the bipolar disorder risk variant SNP rs1006737 in CACNA1C (P=0.020, odds ratio=1.10); and (c) lack of support for rs2251219, a SNP identified in a meta-analysis of affective disorder studies (P=0.51). We estimate that sample sizes 1.8- to 2.4-fold greater are needed for association studies of MDD compared with those for schizophrenia to detect variants that explain the same proportion of total variance in liability. Larger study cohorts characterized for genetic and environmental risk factors accumulated prospectively are likely to be needed to dissect more fully the etiology of MDD.
We present a statistical analysis of the first four seasons from a second-generation microlensing survey for extrasolar planets, consisting of near-continuous time coverage of 8 deg to the 2nd power ...of the Galactic bulge by the Optical Gravitational Lens Experiment (OGLE), Microlensing Observations in Astrophysics (MOA), and Wise microlensing surveys. During this period, 224 microlensing events were observed by all three groups. Over 12% of the events showed a deviation from single-lens microlensing, and for approx. 1/3 of those the anomaly is likely caused by a planetary companion. For each of the 224 events, we have performed numerical ray-tracing simulations to calculate the detection efficiency of possible companions as a function of companion-to-host mass ratio and separation. Accounting for the detection efficiency, we find that 55 +34 -22%of microlensed stars host a snowline planet. Moreover, we find that Neptune-mass planets are approx.10 times more common than Jupiter-mass planets. The companion-to-host mass-ratio distribution shows a deficit at q approx. 10 (exp -2), separating the distribution into two companion populations, analogous to the stellar-companion and planet populations, seen in radial-velocity surveys around solar-like stars. Our survey, however, which probes mainly lower mass stars, suggests a minimum in the distribution in the super-Jupiter mass range, and a relatively high occurrence of brown-dwarf companions.
We report two microlensing planet candidates discovered by the Korea Microlensing Telescope Network (KMTNet) survey in 2017. However, both events have the 2L1S/1L2S degeneracy, which is an obstacle ...to claiming the discovery of the planets with certainty unless the degeneracy can be resolved. For KMT-2017-BLG-0962, the degeneracy cannot be resolved. If the 2L1S solution is correct, KMT-2017-BLG-0962 might be produced by a super Jupiter-mass planet orbiting a mid-M-dwarf host star. For KMT-2017-BLG-1119, the light-curve modeling favors the 2L1S solution but higher-resolution observations of the baseline object tend to support the 1L2S interpretation rather than the planetary interpretation. This degeneracy might be resolved by a future measurement of the lens-source relative proper motion. This study shows that the problem of resolving 2L1S/1L2S degeneracy exists over a much wider range of conditions than those considered by the theoretical study of Gaudi (1998).
In this paper, we describe the first data release of the Visible and Infrared Survey Telescope for Astronomy (VISTA) Deep Extragalactic Observations (VIDEO) survey. VIDEO is a ∼12 deg2 survey in the ...near-infrared Z, Y, J, H and K
s bands, specifically designed to enable the evolution of galaxies and large structures to be traced as a function of both epoch and environment from the present day out to z = 4, and active galactic nuclei (AGNs) and the most massive galaxies up to and into the epoch of reionization. With its depth and area, VIDEO will be able to fully explore the period in the Universe where AGN and starburst activity were at their peak and the first galaxy clusters were beginning to virialize. VIDEO therefore offers a unique data set with which to investigate the interplay between AGN, starbursts and environment, and the role of feedback at a time when it was potentially most crucial.
We provide data over the VIDEO-XMM3 tile, which also covers the Canada-France-Hawaii Telescope Legacy Survey Deep-1 field (CFHTLS-D1). The released VIDEO data reach a 5σ AB-magnitude depth of Z = 25.7, Y = 24.5, J = 24.4, H = 24.1 and K
s = 23.8 in 2 arcsec diameter apertures (the full depth of Y = 24.6 will be reached within the full integration time in future releases). The data are compared to previous surveys over this field and we find good astrometric agreement with the Two Micron All Sky Survey, and source counts in agreement with the recently released UltraVISTA survey data. The addition of the VIDEO data to the CFHTLS-D1 optical data increases the accuracy of photometric redshifts and significantly reduces the fraction of catastrophic outliers over the redshift range 0 < z < 1 from 5.8 to 3.1 per cent in the absence of an i-band luminosity prior. However, we expect that the main improvement in photometric redshifts will come in the redshift range 1 < z < 4 due to the sensitivity to the Balmer and 4000 Å breaks provided by the near-infrared VISTA filters. All images and catalogues presented in this paper are publicly available through ESO's phase 3 archive and the VISTA Science Archive.
Summary Objective To develop concise, up-to-date, patient-focused, evidence-based, expert consensus guidelines for the management of knee osteoarthritis (OA), intended to inform patients, physicians, ...and allied healthcare professionals worldwide. Method Thirteen experts from relevant medical disciplines (primary care, rheumatology, orthopedics, physical therapy, physical medicine and rehabilitation, and evidence-based medicine), three continents and ten countries (USA, UK, France, Netherlands, Belgium, Sweden, Denmark, Australia, Japan, and Canada) and a patient representative comprised the Osteoarthritis Guidelines Development Group (OAGDG). Based on previous OA guidelines and a systematic review of the OA literature, 29 treatment modalities were considered for recommendation. Evidence published subsequent to the 2010 OARSI guidelines was based on a systematic review conducted by the OA Research Society International (OARSI) evidence team at Tufts Medical Center, Boston, USA. Medline, EMBASE, Google Scholar, Web of Science, and the Cochrane Central Register of Controlled Trials were initially searched in first quarter 2012 and last searched in March 2013. Included evidence was assessed for quality using Assessment of Multiple Systematic Reviews (AMSTAR) criteria, and published criticism of included evidence was also considered. To provide recommendations for individuals with a range of health profiles and OA burden, treatment recommendations were stratified into four clinical sub-phenotypes. Consensus recommendations were produced using the RAND/UCLA Appropriateness Method and Delphi voting process. Treatments were recommended as Appropriate, Uncertain, or Not Appropriate, for each of four clinical sub-phenotypes and accompanied by 1–10 risk and benefit scores. Results Appropriate treatment modalities for all individuals with knee OA included biomechanical interventions, intra-articular corticosteroids, exercise (land-based and water-based), self-management and education, strength training, and weight management. Treatments appropriate for specific clinical sub-phenotypes included acetaminophen (paracetamol), balneotherapy, capsaicin, cane (walking stick), duloxetine, oral non-steroidal anti-inflammatory drugs (NSAIDs; COX-2 selective and non-selective), and topical NSAIDs. Treatments of uncertain appropriateness for specific clinical sub-phenotypes included acupuncture, avocado soybean unsaponfiables, chondroitin, crutches, diacerein, glucosamine, intra-articular hyaluronic acid, opioids (oral and transdermal), rosehip, transcutaneous electrical nerve stimulation, and ultrasound. Treatments voted not appropriate included risedronate and electrotherapy (neuromuscular electrical stimulation). Conclusion These evidence-based consensus recommendations provide guidance to patients and practitioners on treatments applicable to all individuals with knee OA, as well as therapies that can be considered according to individualized patient needs and preferences.
ABSTRACT We report the results of the statistical analysis of planetary signals discovered in MOA-II microlensing survey alert system events from 2007 to 2012. We determine the survey sensitivity as ...a function of planet-star mass ratio, q, and projected planet-star separation, s, in Einstein radius units. We find that the mass-ratio function is not a single power law, but has a change in slope at q ∼ 10−4, corresponding to ∼20 M⊕ for the median host-star mass of ∼0.6 . We find significant planetary signals in 23 of the 1474 alert events that are well-characterized by the MOA-II survey data alone. Data from other groups are used only to characterize planetary signals that have been identified in the MOA data alone. The distribution of mass ratios and separations of the planets found in our sample are well fit by a broken power-law model of the form for q > qbr and for q < qbr, where qbr is the mass ratio of the break. We also combine this analysis with the previous analyses of Gould et al. and Cassan et al., bringing the total sample to 30 planets. This combined analysis yields , n = −0.93 0.13, , and for qbr 1.7 × 10−4. The unbroken power-law model is disfavored with a p-value of 0.0022, which corresponds to a Bayes factor of 27 favoring the broken power-law model. These results imply that cold Neptunes are likely to be the most common type of planets beyond the snow line.
We report the discovery of a sub-Jupiter-mass planet orbiting beyond the snow line of an M dwarf most likely in the Galactic disk as part of the joint Spitzer and ground-based monitoring of planetary ...microlensing anomalies toward the Galactic bulge. Most of the microlensing parameters are strongly constrained by the light-curve modeling, and in particular there is a Spitzer-based measurement of the microlens parallax, πE. However, there are no caustic crossings, so the angular Einstein radius has only an upper limit based on the light-curve modeling alone. Additionally, the analysis leads us to identify eight degenerate configurations: the fourfold microlensing parallax degeneracy being doubled by a degeneracy in the caustic structure present at the level of the ground-based solutions. To calculate the physical parameters, and at the same time to break the parallax degeneracy, we make use of a series of arguments: the χ2 hierarchy, the Rich argument (stating that the small-parallax solution is more likely), and a prior Galactic model. The preferred configuration, favored by a likelihood ratio of at least 4000, is for a host at with mass , orbited by a Saturn-like planet with at projected separation , about 2.1 times beyond the system snow line. Therefore, it adds to the growing population of sub-Jupiter planets orbiting beyond the snow line of M dwarfs discovered by microlensing. Based on the rules of the real-time protocol for the selection of events to be followed up with Spitzer, this planet will not enter the sample for measuring the Galactic distribution of planets.
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